The K22 award proposal is for four years of the faculty transition phase at the University of Connecticut Health Center (UCHC) School of Dental Medicine. The candidate received his clinical certificate in Orthodontics and PhD from UCHC. Afterwards, he completed three years of postdoctoral training at the NIDCR. He is currently an Assistant Professor in the Division of Orthodontics at UCHC. This award will enable the candidate to achieve his immediate career objective, which is to develop a successful R01 grant application. This will in turn enable him to achieve his long term goal, which is to develop a well-funded research program that studies the molecular and cellular signaling pathways involved on the application of mechanical loading to craniofacial structures and being able to translate these basic research findings into clinical applications. Substantial shared resources at UCHC, including the Microtomography Facility, the Center for Biomedical Imaging Technology, and the Central Electron Microscope Facility are all available to the candidate. A strong institutional commitment to the candidate's career development in the form of protection of time and start up costs are in place. In addition, the candidate has assembled an advisory committee of well established scientists to monitor his research and career development progress. The goal of the research project is to prevent temporomandibular joint osteoarthritis (TMJ-OA) by detecting and treating it at an early stage. The candidate proposes to use the double biglycan/fibromodulin deficient mice as a model of TMJ-OA to determine biomarkers and mediators of TMJ-OA and to evaluate how mechanical loading affects the progression of TMJ-OA. The specific aims are 1. Determine if osteoarthritis of the temporomandibular joint has similar biomarkers as osteoarthritis of articular hyaline cartilage. 2. Examine changes in apoptosis and proliferation in the superficial articular zone of the mandibular condylar cartilage during osteoarthritis. 3. Determine if decreased mechanical loading can inhibit the progression of TMJ-OA. It is estimated that 1-2 million people in the United States suffer from TMJ-OA. Currently, the treatment modalities for TMJ-OA only involve palliative relief of the symptoms. Greater understanding on the role of mechanical loading in the progression of TMJ-OA and the development of specific biomarkers for TMJ-OA may lead to new treatment modalities for patients who suffer from TMJ-OA. [unreadable] [unreadable] [unreadable]